The functionalization of biomaterials with tissue regeneration-relevant growth factors and cell surface-recognizing antibodies is a rapidly growing area in drug delivery, tissue engineering and regenerative medicine in general. The therapeutic value of these biomaterials is increased by their ability to target specific tissues, cells or disease site, through the surface modification of the carrier with specific molecules, which specifically bind to the cancerous tissues and cells. For example, monoclonal antibodies may be linked to the surface of the carrier and act against antigens on target cells. Among these biomaterials, silk fibroin is recognized as versatile and useful FDA-approved biomaterial that can be utilized for drug delivery. Silk fibroin can be coupled with various biomolecules, such as bone morphogenetic protein 2 to induce bone formation, or RGD peptide to promote cell attachment, via carbodiimide-mediated reactions. Direct covalent coupling may negatively impact the bioactivity of the biomolecules, however, due to the reactions at amine groups. Hence, there is a need for a new strategy to bind bioactive molecules to silk that not only reduces the activity loss of bioactive molecules, but also increases the binding specificity and efficiency.
Further, the current functionlization techniques are mainly surface functionalization of polymerized material by simply immersing the material in the solution or solvent containing the functional group. Incorporation of functional groups within a bulk material, however, is superior to the surface functionalization in many applications. For example, in cartilage and soft tissue engineering applications, functionalization of the bulk material enables encapsulated cells to grow and differentiate in a sustained and homogeneous manner under the support of surrounding high-density functional groups in three dimensions. Hence it is desirable to functionalize the silk in a manner so that it may be further fabricated into different material formats, such as hydrogels, nano/microparticles, as useful scaffolds for encapsulation and delivery of cells or active agents.